Because neutrophil
proteinases such as
elastase and
cathepsin G are considered to play a major role in inflammatory tissue damage, the microcirculatory effect of the
serine proteinase inhibitor (
serpin)
Lex032 after
ischemia/reperfusion (I/R)-induced
pancreatitis was investigated.
Lex032 inhibits these
proteinases by recombinant combination of alpha(1)-antitrypsin and
alpha(1)-antichymotrypsin. Twenty-eight anesthetized rats received either
Lex032 or NaCl 0.9% as a control
solution during baseline conditions or after 1 h of complete reversible
ischemia induced by microclip occlusion of the pancreatic arteries. The number of erythrocyte-perfused capillaries (functional capillary density) and the leukocyte adherence in postcapillary venules were assessed by intravital microscopy 45, 90, and 120 min after administration. In the baseline group,
Lex032 increased leukocyte adherence compared with the NaCl 0.9% baseline group, without changing any other parameter. I/R without Lex-032 treatment resulted in a 50% reduction in functional capillary density, a 2-fold increase in leukocyte adherence, an increase in
interleukin-6 serum concentration, and a significant fall in blood pressure during reperfusion time compared with baseline animals. Treatment with
Lex032 in I/R resulted in significant preservation of capillary perfusion, an absence of
interleukin-6 increase, and preservation of mean arterial pressure during reperfusion time, without changing the leukocyte adherence, compared with the NaCl 0.9% I/R group. Because of its considerable amelioration of microcirculatory perfusion,
Lex032 might be useful in the treatment of pancreatic I/R tissue damage (e.g., cardiac bypass surgery,
pancreas transplantation, and
hemorrhagic shock) by prevention of capillary perfusion failure.